Influence of Gut Microbiota on Progression to Tuberculosis Generated by High Fat Diet-Induced Obesity in C3HeB/FeJ Mice

Front Immunol. 2019 Oct 18:10:2464. doi: 10.3389/fimmu.2019.02464. eCollection 2019.

Abstract

The administration of a high fat content diet is an accelerating factor for metabolic syndrome, impaired glucose tolerance, and early type 2 diabetes. The present study aims to assess the impact of a high fat diet on tuberculosis progression and microbiota composition in an experimental animal model using a C3HeB/FeJ mouse strain submitted to single or multiple consecutive aerosol infections. These models allowed us to study the protection induced by Bacillus Calmette-Guérin vaccination as well as by the natural immunity induced by chemotherapy after a low dose Mycobacterium tuberculosis infection. Our results show that a high fat diet is able to trigger a pro-inflammatory response, which results in a faster progression toward active tuberculosis and an impaired protective effect of BCG vaccination, which is not the case for natural immunity. This may be related to dysbiosis and a reduction in the Firmicutes/Bacteroidetes ratio in the gut microbiota caused by a decrease in the abundance of the Porphyromonadaceae family and, in particular, the Barnesiella genus. It should also be noted that a high fat diet is also related to an increase in the genera Alistipes, Parasuterella, Mucispirillum, and Akkermansia, which have previously been related to dysbiotic processes. As diabetes mellitus type 2 is a risk factor for developing tuberculosis, these findings may prove useful in the search for new prophylactic strategies for this population subset.

Keywords: BCG; C3HeB/FeJ; comorbidity; gut microbiota; high fat diet; mice; obesity; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BCG Vaccine / administration & dosage
  • Bacteria / classification
  • Bacteria / genetics
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Disease Progression
  • Dysbiosis / complications
  • Dysbiosis / microbiology
  • Dysbiosis / physiopathology*
  • Gastrointestinal Microbiome / physiology*
  • Kaplan-Meier Estimate
  • Mice, Inbred Strains
  • Mycobacterium tuberculosis / physiology
  • Obesity / complications
  • Obesity / etiology
  • Obesity / physiopathology*
  • RNA, Ribosomal, 16S / genetics
  • Sequence Analysis, DNA
  • Tuberculosis / complications
  • Tuberculosis / microbiology
  • Tuberculosis / physiopathology*

Substances

  • BCG Vaccine
  • Cytokines
  • RNA, Ribosomal, 16S